Uncovering Heterogeneous Effects via Localized Feature Selection

Liu, X.; Gu, J.; Chen, Z.; Chu, B.; Liu, L.; Morrison, T.; Butler, R. R.; Edelson, J.; Li, J.; Longo, F. M.; Tang, H.; Ionita-laza, I.; Sabatti, C.; Candes, E.; He, Z.

doi:10.1101/2025.06.03.657761

bioRxiv · 10.1101/2025.06.03.657761

Uncovering Heterogeneous Effects via Localized Feature Selection

Liu, X.·Gu, J.·Chen, Z.·Chu, B.·Liu, L.·Morrison, T.·Butler, R. R.·Edelson, J.·Li, J.·Longo, F. M.·Tang, H.·Ionita-laza, I.·Sabatti, C.·Candes, E.·He, Z.

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Abstract

Identifying features that interact to trigger disease, while accounting for heterogeneity across diverse populations, is essential for the development of precision and targeted medicine. Despite the availability of vast and complex health-related datasets, most existing works focus on identifying disease-associated features at the population level or within a few subpopulations, often overlooking individual-level heterogeneity within these groups. To address this limitation, we propose a novel framework that utilizes localized test statistics to identify disease-associated features tailored to individual profiles. Our method leverages the recently developed knockoffs methodology to control the noise level of the selection set so that the results are replicable. Moreover, it allows for the discovery of hidden heterogeneous effects within the data, as demonstrated in an application to single-cell RNA sequencing data for Alzheimers disease. By aggregating localized feature selection results, our framework also enables powerful population-level feature selection. Our framework provides a powerful tool for exploratory studies of precision medicine, offering the potential to generate novel hypotheses for confirmatory biological experiments.

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Liu, X., Gu, J., Chen, Z., Chu, B., Liu, L., Morrison, T., Butler, R. R., Edelson, J., Li, J., Longo, F. M., Tang, H., Ionita-laza, I., Sabatti, C., Candes, E., He, Z.. 2025-06-09. Uncovering Heterogeneous Effects via Localized Feature Selection. https://doi.org/10.1101/2025.06.03.657761

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